The apicomplexan protozoans Cryptosporidium parvum and Toxoplasma gondii are ubiquitous parasites that infect humans and domesticated animals. Recently C. hominus was recognized to be distinct from C. parvum, and does not appear to infect domesticated animals, but rather appears limited to human infections. C. parvum and C. hominus are infectious parasites of major health concern in humans as they are a common cause of illness transmitted by water. C. parvum and C. hominus infections result in debilitating diarrhea that can be life-threatening in immunocompromised patients.
Recent studies have implicated Cryptosporidium spp. in around 15-20% of childhood diarrheal disease in the developing world. Currently, nitazoxanide is the only approved therapy for cryptosporidiosis but it is expensive and has not been shown to be effective in treating immunocompromised hosts. T. gondii may be the most common infectious eukaryotic parasite in humans, based on sero-surveys. Transmitted primarily through undercooked meat or accidental ingestion of cat feces, T. gondii infection presents major health concerns in immunocompromised hosts, where it causes toxoplasmic encephalitis, and in pregnancy, where it can result in severe birth defects or miscarriage.
Sulfadiazine and pyrimethamine are the current therapies for toxoplasmosis, but they can cause nephrotoxicity, rash, and additional complications in pregnancy. Thus, new therapies for treating infections caused by both parasites are greatly needed. In T. gondii, calcium-regulated signaling is associated with a number of cellular functions such as secretion, gliding motility and host cell invasion. The proper control of intracellular calcium levels is important for host cell invasion and T. gondii use several mechanisms for the uptake and release of calcium. Furthermore, this organism contains specialized calcium-regulated signaling enzymes, including a unique family of calciumdependent protein kinases (CDPKs) which are present in plants, ciliates and green algae but not in animals. These kinases are believed to be mediators of secretion, invasion, and gliding motility. T. gondii, C. parvum, and C. hominus are highly related obligate intracellular parasites. While much less is known about the role of calcium signaling in C. parvum and C. hominus, it appears that many calcium-regulated signaling processes are conserved from T. gondii to C. parvum. C. parvum and C. hominus also possess CDPKs that are believed to play important roles in calcium-regulated processes and they are virtually identical in these two spp. Thus, inhibitors of C. parvum CDPKs would be expected to inhibit C. hominus CDPK.